P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes

Arterioscler Thromb Vasc Biol. 1997 Feb;17(2):310-6. doi: 10.1161/01.atv.17.2.310.

Abstract

The accumulation of monocyte/macrophages and T lymphocytes in arterial intima is a hallmark of early atherogenesis. To investigate the temporal relationships between endothelial expression of adhesion molecules (eg, P-selectin and vascular cell adhesion molecule-1 [VCAM-1]) and intimal accumulation of macrophages and T lymphocytes, immunostaining was performed by using serial frozen sections from intercostal branch points of thoracic aortas of New Zealand White rabbits that had been fed a 0.3% cholesterol diet. After 1 week of cholesterol feeding, neither macrophages nor T lymphocytes were detected, although endothelial expression of P-selectin and VCAM-1 was observed. After 3 weeks, macrophages were detectable in 75% and T lymphocytes were present in 25% of the rabbits. Expression of P-selectin and VCAM-1 was sustained until 10 weeks. Infiltration of T lymphocytes was restricted in areas in which macrophages were accumulated and did not appear to precede macrophage infiltration. E-selectin expression was not detectable before accumulation of mononuclear leukocytes; however, very few endothelial cells covering foam cell lesions expressed E-selectin after 6 weeks. Similar results were obtained in Watanabe heritable hyperlipidemic rabbits aged 1, 2, and 3 months. Taken together, localized expression of P-selectin and VCAM-1 may play a key role in the initial recruitment of macrophages and T lymphocytes in early atherogenesis.

MeSH terms

  • Animals
  • Aorta / metabolism*
  • Aorta / pathology*
  • Cholesterol, Dietary / pharmacology
  • E-Selectin / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endotoxins / pharmacology
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / pathology*
  • Macrophages / pathology
  • Male
  • P-Selectin / metabolism*
  • Rabbits
  • T-Lymphocytes / pathology
  • Tunica Intima / pathology*
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Cholesterol, Dietary
  • E-Selectin
  • Endotoxins
  • P-Selectin
  • Vascular Cell Adhesion Molecule-1